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1.
Toxins (Basel) ; 9(11)2017 10 25.
Article in English | MEDLINE | ID: mdl-29068360

ABSTRACT

Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L, as consequence of Stx-induced endothelium damage, participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.


Subject(s)
CD40 Ligand/blood , Endothelial Cells/drug effects , Hemolytic-Uremic Syndrome/blood , Shiga Toxin/toxicity , Cells, Cultured , Child , Child, Preschool , Endothelial Cells/pathology , Female , Hemolytic-Uremic Syndrome/chemically induced , Humans , Infant , Kidney/metabolism , Kidney/pathology , Male , Microvessels , Monocytes/metabolism , Oxidative Stress , Platelet Activation/drug effects , Reactive Oxygen Species/metabolism
2.
Vaccine ; 34(39): 4732-4737, 2016 09 07.
Article in English | MEDLINE | ID: mdl-27527816

ABSTRACT

Shiga toxin producing Escherichia coli (STEC) are bacterial pathogens involved in food-borne diseases. Shiga toxin (Stx) is the main virulence factor of STEC and is responsible for systemic complications including Hemolytic Uremic Syndrome (HUS). It has been previously demonstrated that Shiga toxin type 2 (Stx2) induces pregnancy loss in rats in early stage of pregnancy. The main purpose of this study was to determine if an active immunization prevents Stx2 mediated pregnancy loss and confers passive protective immunity to the offspring. For that purpose Sprague Dawley female rats were immunized with the chimera based on the enzyme lumazine synthase from Brucella spp. (BLS) and the B subunit of Shiga toxin 2 (Stx2B) named BLS-Stx2B. After immunization females were mated with males. At day 8 of gestation, dams were challenged intraperitoneally with a sublethal and abortifacient dose of Stx2. The immunization induced high anti-Stx2B-specific antibody titers in sera and most important, prevented pregnancy loss. Pups born and breastfeed by immunized dams had high anti-Stx2B-specific antibody titers in sera. Cross-fostering experiments indicated that passive protective immunity against Stx2 was transmitted through lactation. These results indicate that immunization of adult female rats with BLS-Stx2B prevents Stx2-induced pregnancy loss and confers anti Stx2 protective immunity to the offspring.


Subject(s)
Abortion, Spontaneous/prevention & control , Escherichia coli Infections/prevention & control , Escherichia coli Vaccines/immunology , Immunity, Maternally-Acquired , Shiga Toxin 2/immunology , Abortion, Spontaneous/microbiology , Animals , Antibodies, Bacterial/blood , Antibodies, Neutralizing/blood , Brucella/enzymology , Female , Foodborne Diseases/prevention & control , Hemolytic-Uremic Syndrome/prevention & control , Male , Multienzyme Complexes/immunology , Pregnancy , Rats , Rats, Sprague-Dawley , Recombinant Fusion Proteins/immunology , Shiga-Toxigenic Escherichia coli
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